This study aims at identifying common pathogenic somatic mutations at different stages of colorectal carcinogenesis in Egyptian patients. Our cohort included colonoscopic biopsies collected from 120 patients: 20 biopsies from patients with inflammatory bowel disease, 38 from colonic polyp patients, and 62 from patients with colorectal cancer. On top of this, the cohort included 20 biopsies from patients with non-specific mild to moderated colitis. Targeted DNA sequencing using a customized gene panel of 96 colorectal related genes running on the Ion Torrent NGS technology was used to process the samples. Our results revealed that 69% of all cases harbored at least one somatic mutation. Fifty-seven genes were found to carry 232 somatic non-synonymous variants. The most frequently pathogenic somatic mutations were localized in TP53, APC, KRAS, and PIK3CA. In total, 16 somatic mutations were detected in the CRC group and in either the IBD or CP group. In addition, our data showed that 51% of total somatic variants were CRC-specific variants. The average number of CRC-specific variants per sample is 2.4. The top genes carrying CRC-specific mutations are APC, TP53, PIK3CA, FBXW7, ATM, and SMAD4. It seems obvious that TP53 and APC genes were the most affected genes with somatic mutations in all groups. Of interest, 85% and 28% of the APC and TP53 deleterious somatic mutations were located in Exon 14 and Exon 3, respectively. Besides, 37% and 28% of the total somatic mutations identified in APC and TP53 were CRC-specific variants, respectively. Moreover, we identified that, in 29 somatic mutations in 21 genes, their association with CRC patients was unprecedented. Ten detected variants were likely to be novel: six in PIK3CA and four variants in FBXW7. The detected P53, Wnt/βcatenin, Angiogenesis, EGFR, TGF-β and Interleukin signaling pathways were the most altered pathways in 22%, 16%, 12%, 10%, 9% and 9% of the CRC patients, respectively. These results would contribute to a better understanding of the colorectal cancer and in introducing personalized therapies for Egyptian CRC patients.
Background: Colorectal cancer (CRC) incidence is progressively increasing in Egypt. Unfortunately, there is inadequate knowledge of the acquired somatic mutations in Egyptian CRC patients which limit our understanding of its progression. To the best of our knowledge, our study is the first to sequence multiple-gene panel to identify the somatic mutation pattern associated with CRC disease progression in a cohort of Egyptian patients. Custom 72 genes, which are frequently associated with CRC, were sequenced using Qiaseq UMI-based targeted DNA panel in 120 fresh tissues classified into; inflammatory bowel disease (IBD; n=20), colonic polyp (CP; n=38) and CRC (n=62) as well as 20 biopsies with non-specific colitis served as a control group (n=20). Results: Using Ingenuity Variant Analysis (IVA), we revealed that APC, TP53 & ATM genes harbored the highly frequent CRC-specific somatic mutations (15, 11 & 6, respectively). We also identified common somatic mutations (predictors) that were associated with disease progression from colitis to CRC; APC (c.1742delA (65%)), TP53 (c.121delG (58%), c.215C>G (52%)), ATM (c.640delT (16%)), IGF2 (c.677delG (56%)), RET (c.2071G>A (37%)), ACVR2A (c.1310delA (26%)), PIK3CA (c.1173A>G (16%)) & KIT (c.1621A>C (13%)). Furthermore, pathway analysis using Ingenuity Pathway Analysis (IPA) showed that Wnt/βcatenin, ATM signaling, RTK-RAS and TGF-β were the most altered pathways in the CRC group (73%. 72%, 40% & 36%, respectively).Conclusion: In this data set, we shed the light on the most frequent somatic mutations and the most altered pathways that are crucial for understanding colorectal cancer predisposition and developing personalized therapies for the Egyptian CRC patients.
A sandy clay loam soil was used to study the effect of (a) urea application at rates equivalent to 250, 500, 1000 and 2000 ppm‐N, at moisture content level of 100 % WHC, and (b) soil moisture levels of 30, 60 and 100 % of the WHC in addition to water‐logging conditions, when urea was applied at the rate of 500 ppm‐N, on urea‐N transformations. In both cases, the incubation took place at 30°C and lasted for 6 weeks. The experiments were carried out in a closed system daily aerated. Complete hydrolysis of the added urea was attained after 1, 2 and 3 weeks for 250, 500 and 1000 ppm urea‐N, respectively. Six weeks incubation period was not enough for full hydrolysis of the 2000 ppm urea‐N. The rate of urea hydrolysis increased linearly for urea concentration up to 1000 ppm N. This concentration must have been sufficient to saturate the urease present in the soil used. The peak of NO 2−N was higher the higher the rate of urea applied. Delay of the nitrate formation was always accompanied by the accumulation of nitrites. At the end of the experiment, the nitrate‐N formed represented 93,90,77 and only 20 % of the initially applied nitrogen for 250, 500, 1000 and 2000 ppm‐urea‐N, respectively. The rate as well as the total ammonia loss increased with increasing the rate of urea application. No appreciable differences were observed in urea hydrolysis due to the variations in moisture levels within the range of WHC. Under water‐logging conditions, urea hydrolysis was slower and extended to the 6th week, also the rate of urea hydrolysis was no more than 50 % of the rate produced in moisture treatments within WHC. NO 2−N accumulation persisted for one week in the moisture levels within the range of WHC, while it continued in the water‐logged treatment till the end of the experiment. Nitrate formation was slightly favoured at 100 % WHC and decreased somewhat with lowering the soil moisture levels. However, it was completely inhibited under water‐logging conditions. Ammonia volatilization was not markedly affected by moisture levels within WHC, however, the water‐logged treatment showed the highest total loss.
A field experiment on an alluvial clay loam soil at Giza revealed that the dry matter yield, as well as N and P uptake of Ammi vbnugu fruits or herb were significantly increased with nitrogen application up to 60 kg Nha. P application up to 30 kg P205ha significantly increased the dry matter yield and the uptake of N and P of herb, but did not significantly affect those of fruits. At maturity, most, if not all, chromones rest in the fruits. The concentration in herb (Stems + rays) did not exceed 0.01 %. Higher yields of total chomones, khelling and visnagin in fruits were brought about with nitrogen application at the rate of 60kg Nha. P application tends to increase all these parameter, yet all were nonsignificant. The interacting effect between nitrogen and phosphorus on these characters was insignificant.Plant analysis of leaves, stem, or shoot at 120, 135 and 150 days old plants revealed no relation between phosphorus concentration and final yield. However, nitrogen concentrations provided a good tool to evaluate the nutritional status of the plants. The critical level was 2.75,1.85, or 1.45 % N in shoots of 120, 135, or 150 days old plants. The P % in these shoots was around 0.35-0.50 %. Erh.ag und Chromon-Gehdt von AmmiVisnaga in Beziehung zur Stickstoff-und Phosphor-V e m w o g Ein Feldversuch auf einem alluvialen L-Boden bei Giza ergab, daD der Fruchtertrag und die Nund P-Aufnahme von Ammi visnaga durch gestaffelte N-Gaben bis zu 60 kgha signifikant anstieg. P-Diingung forderte bis zu 30 kg PZOha das Gewicht und die N-und P-Gehalte der Blattmasse, aber nicht die der Friichte. Zur Reife befanden sich die Chromone iiberwiegend in der Frucht; der Gehalt der Blatter blieb unter 0,01%. Der Ertrag an Gesamt-Chromon sowie an Khelling und Visnagin war bei Gaben von 60kgN am hochsten, P-Diingung hatte keine signifikante Wirkung. Auch war die Wechselwirkung zwischen N und P nicht signifikant. Der P-Gehalt der Blltter, Stengel oder Sprosse wies nach 120,135 und 150 Tagen keine Beziehung zum Ertrag auf. Der N-Gehalt der Pflanzen war hingegen ein gutes MaD fiir den Ernahrungszustand der Pflanzen. Der Ertragswert lag bei 2,75; 1,85 und 1,45 % in den Sprossen von 120,135 und 150 Tage alten Pflanzen. Der P-Gehalt bewegte sich dabei zwischen 0,35 und 0,50 %.
Aim: This study aimed to sequence BRCA1 & BRCA2 genes to identify the frequency of the detected genetic mutations in the disease progression of colorectal cancer (CRC) and to estimate colorectal cancer risks in those BRCA mutation carriers. Material and methods: 140 biopsy samples were collected from Egyptian patients categorized into inflammatory bowel disease (IBD) (n=20), colonic polyp (CP) (n=38) and CRC (n=62) patients as well as subjects with chronic colitis served as a control group (n=20). The libraries were performed using Qiaseq UMI-based targeted panel and sequenced via Ion proton sequencer. The detected genetic variants at 500x were annotated against Cosmic, dbSNP, exac all, Polyphen2, Sift and Clinvar databases. Results: Analysis revealed that BRCA1 gene harbored 26, 19, 8 and 11 variants in the CRC, CP, IBD and control groups; respectively. Exon 10 was the most affected exon harbored 7 pathogenic variants in the CRC group. Two out of 7 were the most frequently detected common pathogenic variants associated with disease progression from colitis to CRC (c.1961delA (11%) & c.3214delC (16%). Moreover, 3 common begnin SNP variants were found to be related to ethnicity (c.3548A>G (58%), c.2612C>T (60%), c.4900A>G (69%). Moreover, BRCA2 gene harbored 48, 29, 24 and 18 variants in the CRC, CP, IBD and control groups respectively. Exon 2, 11, 23 were the most affected exons harbored 12 pathogenic variants in the CRC group. Four out of 12 were the most frequently detected common pathogenic variants associated with disease progression from colitis to CRC (c.3860delA (8%), c.5351delA (18%), c.9097delA (24%) & c.36delT (34%). Conclusion: Our data showed that BRCA1 & BRCA2 genes analyzed by Next-Generation Sequencing (NGS) identifies large number of pathogenic and begnin variants that are crucial for understanding CRC predisposition and early detection. Also, developing personalized therapies that efficiently target the individual CRC-specific mutations. Key words: Egyptian Colorectal cancer, BRCA1, BRCA2, pathogenic, begnin, Next Generation Sequencing Citation Format: Amira Salah El-Din Youssef, Ahmed Osama Touny, Zeinab K. Hassan, Mohammed Mohey Eldin, Mai M. Lotfy, Auhood Nassar, Mohamed El-Hadidi, Ali Kishk, ola sayed, Abdel-Rahman N. Zekri. Profiling of BRCA1 & BRCA2 mutations in Egyptian colorectal cancer patients via next generation sequencing [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3615.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.